Glucocorticoids (GC) affect virtually all organ systems, acting mainly via the glucocorticoid receptor (GR). The immune system is the best characterized tissue for assessing GC sensitivity. It is well established that the immune system GC sensitivity varies widely between normal subjects. However, it remains unclear whether measurements of the immune system GC-sensitivity reflect the GC-sensitivity in other GC target tissues of the same individual. Thus, in the present study we compared the GC sensitivity of the immune system, assessed by determining the dexamethasone inhibition of LPS-induced TNF-alpha production in peripheral leukocytes, with the feedback sensitivity of the HPA axis, assessed by a very low dose dexamethasone (0.25 mg) suppression test, in sixteen healthy volunteers. We observed a wide variation in the magnitude of the responses in the two GC targets. However, and in agreement with a number of previous reports, in a given subject the GC sensitivity of the immune system did not correlate with that of HPA axis inhibition, indicating a tissue specificity of GC sensitivity in the same individual. In summary, the bulk of current evidence suggests that GC sensitivity is tissue specific for a given individual. Additional studies are warranted to elucidate the exact mechanism(s) involved in the differential GC tissue responsiveness.

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